The Parent Plant 15 



This intorniation lias been linked with nuxlei n concepts ol specific 

 biological activity associated with certain chemical structures.^ The 

 .Svnii)osiuni on the Chemistry ot Colchicine at the 1951-52 meeting 

 ol the American Association for the Advancement of Science at Phila- 

 delphia, Pennsylvania, dealt with this problem. 



Advancement was made in colchicine chemistry when Adolph W^in- 

 ilaus. alter a long series of investigations, set forth the concept of a 

 three-ring structure.-^^ l^pon analysis of oxidation products, his case 

 was developed for three rings, A. B, and C:, each constructed of 6 

 carbons, respectively. The first ring A is aromatic, 6 carbon with 

 three associated methoxyl groups. This much of the Windaus formula 

 has l)een confirmed and remains as earlier constructed. •• Other parts 

 required modification as will be shown below and in more detail 

 in Chapter 6. 



l^nusually high water solubility characterizes colchicine in spite 

 of a deficiency of the groups generally associated with this capacity.'^ 

 To account for this feature and others, Dewar speculated that the 

 structural concept should include a "tropolone" system and proposed 

 that ring C was a 7-membered structure.'^ 



Earlier than this projjosal, doubts were raised by Cohen, Cook, 

 and Roe in 1940^ that led to changes in the central part of the struc- 

 ture, ring B. Changing ring B, as well as C, from a 6- to 7-membered 

 ring appeared necessary. This first evidence for the need to modify 

 Windaus" structure, which came from the Clasgow Laboratories,^ has 

 since led to extensive studies dealing with the structure of colchicine. 

 Dr. James Loudon, a member of this team, has generously contributed 

 the chapter on chemistry. Degradative work provided thorough evi- 

 dence that ring B is 7-membered instead of 6 as originally proj^osed. 

 Further confirmation came through synthesis -work-^^ upon dl colchinol 

 methyl ether, also establishing the position of the amino group on 

 ring B. 



A compound described as octahydrodemethoxydesoxydesacetamido- 

 colchicine,-'" has been obtained by degradation. Such a product de- 

 rived from colchicine that is more or less a carbon skeleton for rings 

 B and C presents opportunities for making some definitive proof of 

 the structure of colchicine through synthesis. 



Tropolone, as originally suggested by Dewar has been synthesized;!^ 

 therefore, ring C of colchicine is essentially as jiredicted in earlier 

 sjK'c ulations. Much might be expected here for biological experi- 

 mental procedures. Interesting tests with trojjolonoid compounds 

 have been tried. 1 he "radiomimetic" action of a tropolonoid com- 

 pound is of considerable interest.^"' 



Polarographic evidence supjjorts the work with colchicine and 

 deri\ati\es in several aspects.-'" Santavy and associates beginning in 



